PT  - JOURNAL ARTICLE
AU  - Schwantes, Astrid
AU  - Specht, Rachel
AU  - Chen, Qi
TI  - Proceedings of 2017 Viral Clearance Symposium Session 4: Submission Strategies
AID  - 10.5731/pdajpst.2018.009142
DP  - 2018 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2018.009142
4099  - http://journal.pda.org/content/early/2018/07/03/pdajpst.2018.009142.short
4100  - http://journal.pda.org/content/early/2018/07/03/pdajpst.2018.009142.full
AB  - Appropriate performance of virus validation studies and testing of unprocessed bulk harvests for retrovirus particle count are procedures in the demonstration of an acceptable level of viral safety for cell-derived biotechnology products. Product-specific validation studies on virus reduction with two model viruses (usually MuLV and a parvovirus) performed in duplicate runs is standard for clinical trial applications. For the retroviral safety margin normally a 6 log reduction is expected. Retroviral particle counts are measured traditionally by transmission electron microscopy (TEM) and are commonly performed at contract laboratories. These procedures are quite time consuming and can be associated with significant costs. In particular the time factor is a hurdle for companies to bring their new products fast to the clinic. In this session, several strategies were presented how to lower time, costs and work load in the evaluation of viral safety for early clinical trial applications while still ensuring sufficient level of viral safety of the product. In addition, virus reduction strategies for molecules which do not have the standard antibody structure are presented. The feasibility of the use of retrovirus-like particle (RVLP) in pre-validation of virus removal is investigated and the use of quantitative polymerase chain reaction (qPCR) as alternative to infectivity assays in virus validation studies as well as its use as alternative to quantitative TEM analysis for determining RVLP count in the bulk harvest of a perfusion bioreactor is presented in this session.